Policies, Procedures and Guidance

GIM 36 – Human Embryonic Stem Cell Research Policy and Guidelines

Contents

SUBJECT: Policy and Guidelines for the Conduct of Research Involving the Use of Human Embryonic Stem Cells

Effective: November 14, 2008

Background

On August 9, 2001, President George W. Bush announced that federal funding could be used to support human embryonic stem cell research but only with respect to stem cell lines that had already been derived as of that date. The announcement stated that use of federal funds would be limited to research on existing stem cell lines that were derived:

with the informed consent of the donors,

from excess embryos created solely for reproductive purposes, and

without any financial inducements to the donors.

In addition, the announcement expressly stated that no federal funds could be used for:

the derivation or use of stem cell lines derived from newly destroyed embryos,

the creation of any human embryos for research purposes, or

the cloning of human embryos for any purpose.

President Bush also stated that in order to ensure that federal funds were used to support only stem cell research that is scientifically sound, legal, and ethical, he was directing the National Institutes of Health to examine the derivation of all existing stem cell lines in order to create a registry of those lines that satisfy these criteria.

Subsequent to August 9, 2001, the National Institutes of Health established a human embryonic stem cell registry listing those stem cell lines that are eligible for federal funding support. Human embryonic cell lines not currently listed in the registry are considered “ineligible” and may not be used in federally funded research. Except for the prohibition against use of federal funds for research using ineligible stem cells, the federal government does not otherwise restrict research involving the use of ineligible cell lines. As a result, research utilizing cell lines not listed on the registry may be conducted at institutions receiving federal support providing the research is supported solely by non-federal funds. To comply with federal requirements, institutions that receive federal research support must have adequate controls to assure that no federal funds are expended, either directly or indirectly, in support of the ineligible research. In order to accomplish this, researchers and institutions must carefully monitor costs, expenditures and use of resources in a manner that assures that expenditures for this ineligible research are treated as “unallowable” under applicable federal accounting rules.

As research with human embryonic lines has increased, there has been a recognition within the research community that additional guidelines were needed, partly to address the lack of applicable federal regulations for research with ineligible cell lines and partly to address a growing awareness of important scientific and ethical questions in this field. As a result of these concerns, the National Research Council and the Institute of Medicine of the National Academies established the “Committee on Guidelines for Human Embryonic Stem Cell Research” whose purpose was to review this field of research and to develop appropriate recommended guidelines. In April 2005, the National Academies published a major report, (amended in 2007) entitled “Guidelines for Human Embryonic Stem Cell Research” which provides an ethical and legal framework for the responsible conduct of all human embryonic stem cell research. The fundamental recommendation of the amended report is the establishment of oversight through a local committee that is charged with reviewing and approving research protocols. The committee does not replace an institution’s local institutional review board having authority over human subjects research, but instead is charged with assurance that the research has scientific and ethical merit and that the provenance of the cells used in the research has been adequately established. The committee’s report also offers guidance for institutional review boards as they consider stem cell research proposals requiring human subjects research review and approval.

The federal requirements and limitations with respect to human embryonic stem cell research and the amended 2005 National Academies guidelines are the foundation of the University’s policy in this area and for GIM 36. GIM 36 sets forth a number of requirements for the conduct of human embryonic stem cell research, including segregation of federal and non-federal funding for research using “ineligible” cell lines and oversight of research through a standing committee.

General Policy

The University of Washington believes that research utilizing human embryonic stem cells is essential to expanding fundamental scientific knowledge of cellular and developmental human biology. The University has further concluded that such research offers a significant potential to develop treatments for a large number of serious and debilitating human diseases, disorders and health conditions, including genetic diseases, tissue injuries, and degenerative diseases such as heart disease, spinal cord injuries, and various diseases of the nervous system. It is the University’s policy to permit and encourage qualified investigators to engage in responsible and ethical research requiring the use and derivation of human embryonic stem cells, human embryonic germ cells, and human adult stem cells obtained from any source, providing the cells are obtained and the research is conducted with appropriate oversight and in accordance with all applicable laws, rules and regulations.

Prohibited Activities

The UW has expressly prohibited certain activities relating to human embryonic stem cells, such as human reproductive cloning, which are described in greater detail in the section on Prohibited hESC Activites, below.

Definitions

For purposes of GIM 36, the following definitions shall apply:

adult stem cell

means a lineage-restricted, non-pluripotent stem cell that is capable of giving rise to some, but not all, adult cell types, typically found in the differentiated tissue of an organism.

approved hESC line

means a stem cell line listed and approved on the NIH hESC registry.

blastocyst

means a preimplantation human embryo consisting of approximately 50 to 250 cells generally in the form of a sphere made up of an outer layer of cells, a fluid-filled cavity, and an inner mass of cells.

Chairperson

means the duly-appointed chairperson of the ESCRO Committee.

chimera

means an organism having two or more genetically different cell types, including cell types from one or more species.

chimeric animal

means a nonhuman animal having two or more genetically different cell types, including cell types from one or more species.

chimeric embryo

means an embryo having two or more genetically different cell types, including cell types from one or more species.

cloning

means the asexual production of a line of cells that is genetically identical to the originating cell.

data

mean information or other results arising from research, other than intellectual property.

embryo

means an organism in the early stages of growth and differentiation.

embryonic germ cell

means an ESC-like cell derived from primordial germ cells found in the gonadal ridge of an embryo or fetus.

means laboratory space, offices, and any other locations owned or operated by the UW and used in the conduct of research.

germ cell

means either a sperm or egg haploid cell (gamete) or a cell that typically becomes a gamete.

hESC derivative

means any DNA, RNA, protein, or other biological products secreted by or extracted from a hESC, including an adult stem cell, but does not include any hESC line, hESC derived cell line, data, or intellectual property.

hESC derived cell line

means one or more cells or cell line, including a hESC line created from the destruction of a human embryo, but does not include a hESC line created by SCNT without destruction of a human embryo.

hESC line

means a stem cell line consisting of hESC.

hESC research

means research involving either the use or creation of hESC.

human embryo

means the embryo of a human, generally defined as extending from the time of the formation of the zygote through the end of the first eight weeks after such formation.

human embryonic stem cell(s) or hESC(s)

mean one or more human embryonic stem cells, commonly first derived from the inner cell mass of the blastocyst stage of a human embryo.

human fetus

means the fetus of a human, generally defined as extending from the end of the human embryo to birth.

human subject

means an individual about whom an investigator conducting research obtains (a) data through intervention or interaction with the individual, or (b) identifiable private information.

human subjects research

means research involving human subjects.

induced human pluripotent stem cell

means a human cell formed from a non-embryonic source where pluripotency is established and no human embryo or gametes were destroyed.

ineligible hESC research

means hESC research ineligible for federal support.

Institutional Review Board (IRB)

means an appropriately designated institutional review board designated by the UW to review, approve and monitor in accordance with applicable federal and state law human subjects research occurring at the UW or involving UW personnel.

intact human embryo

means a human embryo that is developing in an integrated, normal fashion and continuing to progress and otherwise capable of progressing into a fully-developed human.

intellectual property

means inventions and discoveries, whether or not patentable, trade secrets, and copyrightable materials, arising from research, including but not limited to new hESC lines and hESC derived lines, hESC derivatives, and valuable methods and tools for conducting hESC research.

investigator

means any person involved in the design, conduct or reporting the results of research.

ISCRM

means the UW’s Institute for Stem Cell and Regenerative Medicine.

NIH hESC registry

means the current list of hESC lines, as it may from time to time be revised, that are eligible for federal funding.

OSP

means the UW’s Office of Sponsored Programs.

personnel

means all persons, including but not limited to investigators, who participate or expect to participate in research, including employees, faculty, post-doctoral fellows and students.

pluripotent stem cell

means a stem cell having the capacity to differentiate into the adult cells of all three primary germ layers.

principal investigator (PI)

means the investigator having overall responsibility for the conduct of a particular research project.

prohibited hESC activities

means those activities, including certain types of research, relating to hESC prohibited by the UW as further described in the section Prohibited hESC Activites of GIM 36.

provenance

means sufficient documentation, based on usual and customary standards within the field of hESC research, to authenticate the history of ownership and place of origin of hESC and/or hESC lines.

reproductive cloning

means the use of cloning for the purpose of creating one or more adult organisms that are all genetically identical to another organism.

research

means a systematic investigation, including development, testing and evaluation, designed to develop or contribute to general knowledge.

SCNT

means somatic cell nuclear transfer, a procedure by which the nucleus of a somatic cell is transferred into a female germ cell (egg), the nucleus of which has been removed.

stem cell

means a cell having the potential for prolonged undifferentiated growth while retaining the potential to differentiate into one or more cell types.

stem cell line

means a mass of cells descended from and retaining the characteristics of an original stem cell.

totipotent stem cell

means a stem cell having the capacity to differentiate into every cell type, including extra-embryonic cells, and to form an entire organism.

University or UW

means the University of Washington.

zygote

means a diploid cell formed by the union of mature female and male germ cells.

Rules, Procedures and Guidance

Legal Compliance

All UW personnel engaged in hESC research and all persons engaged in hESC research utilizing any UW facilities, equipment or other resources shall do so only in compliance with all applicable federal, state, and local laws, regulations, and policies.

Compliance with Applicable UW Policies, Regulations and Procedures

All UW personnel engaged in hESC research and all persons engaged in hESC research utilizing any UW facilities, equipment or other resources shall do so only in compliance with all applicable UW policies, regulations, and procedures, including without limitation GIM 36 and other policies, regulations, and procedures relating to the following:

hESC research

Sponsored research

Human subjects research

Animal research

Conflict of interest

Purchasing

Protection of patient confidential information

Research billing

Time and effort reporting

Intellectual property and technology transfer

Prohibited hESC Activities

No UW personnel shall engage in and no UW facilities, equipment or other resources shall be utilized for any of the following:

Human reproductive cloning;

In vitro culture of an intact human embryo for more than 12 days of development or until formation of the primitive streak, whichever occurs first;

Payment to a donor solely for the purpose of creating a human embryo to be used in hESC research;

Implanting a chimeric embryo containing non-human cells, including ESC, into the uterus of a human;

Implanting a chimeric embryo containing hESC into the uterus of a nonhuman primate and allowing the resulting pregnancy to progress to the point of independent viability;

Breeding of a chimeric animal having hESC that were introduced during any stage of the animal’s embryonic or fetal development;

Breeding of a chimeric animal having hESC where there is a reasonable possibility that human genetic material could be incorporated into the animal’s germ cells;

Using federal funds to engage in ineligible hESC research; or

Engaging in hESC research in a manner that is contrary to any applicable federal, state or local laws, rules or regulations.

ESCRO Committee Review Required

General Rule. Except as provided in the section on Research and Activities Exempt from ESCRO Committee Review below, all hESC research, including research involving the use or creation of a hESC derived cell line, must be reviewed and approved by the ESCRO Committee prior to the commencement of the research.

Full Review. Except for research requiring only minimal review as provided in the following subsection 3, all hESC research requiring review by the ESCRO Committee shall only be approved after due consideration by the ESCRO Committee convened at a regular or special meeting, a quorum being present, called for such purpose. Subject to the prohibitions set forth in the section Prohibited hESC Activites above, examples of research requiring ESCRO Committee review include but are not limited to:

hESC research in which further human consent beyond that already obtained is required;

Creation of a new hESC line or hESC derived cell line by any means, including through use of SCNT, human zygotes, or a human embryo furnished by an in vitro fertilization clinic or other lawful source;

Introduction of hESC into a nonhuman animal;

Research in which personally identifiable information about the donor of hESC is readily ascertainable or may become known;

Minimal Review. The following hESC research may be approved after minimal review by one or more persons delegated authority for such reviews by the ESCRO Committee:

In vitro hESC research utilizing hESC lines that have been pre-approved for such use by the ESCRO Committee;

In vitro hESC research utilizing hESC derived cell lines obtained from hESC lines that have been pre-approved for such use by the ESCRO Committee; and

Other types of hESC research that the Vice Provost for Research has made a written determination, after due consideration of the likely risks and benefits of such research, that such categories are appropriate for minimal review.

Research and Activities Exempt from ESCRO Committee Review

The following Research and/or other activities are not subject to GIM 36 and are exempt from review by the ESCRO Committee.

Research involving use of adult stem cells;

Use of human cord blood;

Transplantation of stem cells as part of recognized and accepted medical treatment for a disease or condition; and

Other categories of hESC research or activities that the Vice Provost for Research has made a written determination, after due consideration of relevant legal and ethical requirements, that such research or activities are appropriate for exemption from ESCRO Committee review.

The creation and ex vivo passage of induced pluripotent stem cells does not require ESCRO committee review. ESCRO review is required if the iPSCs are pluripotent and are transferred into an animal or human, or are used to make an embryo.

Approval of hESC Research – General

All hESC research conducted at the UW that is classified as “Sponsored Research” under Grants Information Memorandum 34 shall be processed through OSP on a Form eGC1. All hESC research conducted at the UW that is not classified as “Sponsored Research” under Grants Information Memorandum 34 shall be processed in accordance with established rules and procedures. hESC research shall only be conducted after all generally required UW approvals have been obtained for such research.

UW Embryonic Stem Cell Research Oversight Committee

Required ESCRO Committee Review and Approval. In order to carry out appropriate institutional oversight of hESC research, including the derivation and use of hESC and the use of human embryos in connection with such research, and in order to comply with all federal and state laws, rules, and regulations and all applicable ethical guidelines and UW policies and procedures, no use of human embryos, including the derivation of hESC from any source, or the use of hESC or human embryos for research or clinical investigation, shall be initiated by or for the UW prior to the review and approval of the proposed research by the UW ESCRO Committee.

Establishment, General Authority and Administrative Support. The UW’s Vice Provost for Research shall establish the ESCRO Committee, which shall have general authority to review, conditionally approve, require modifications of, or disapprove all hESC research proposals at the UW requiring review under GIM 36. The ESCRO Committee may also from time to time advise and make recommendations to the Vice Provost for Research with respect to legal, ethical and policy issues regarding hESC research. The duties and responsibilities of the ESCRO Committee shall be distinct and separate from the UW IRB, and to the extent practical, the subject matter of the reviews by the IRB and ESCRO Committee should not overlap. The UW Office of Research will provide necessary administrative support for the ESCRO Committee.

Membership. The ESCRO Committee shall consist of ten voting members appointed by and serving at the pleasure of the Vice Provost for Research. Members shall serve for renewable terms of three years each, except that the terms of the initial members shall be staggered to the extent practicable. Except for the public representative, all other committee members may be employees of the UW or an institution affiliated with the UW. Appointments to the ESCRO Committee shall be made to persons from a variety of academic and professional fields in order to reflect the scientific, medical and ethical expertise necessary to carry out the committee’s responsibilities. The ESCRO Committee shall consisting of the following:

Chairperson (designated by the Vice Provost for Research for a renewable two-year term);

Two public members not affiliated with the UW;

Administrator or researcher experienced in the regulation and/or oversight of human subjects research;

Expert in medical ethics and/or legal matters; and

Five researchers with terminal degrees and expertise in disciplines related to hESC research, including but not limited to, developmental biology, stem cell research, molecular biology, comparative medicine, and assisted reproduction.

At the discretion of the Vice Provost for Research, one or more of the foregoing five researcher positions may be filled through the appointment of two persons to serve as alternate voting members designated to hold a single position. Alternate voting members shall have similar expertise and share all responsibilities for the position and alternate attendance at meetings of the ESCRO Committee. Alternates shall also be entitled to attend ESCRO Committee meetings in a non-voting capacity, but on such occasions may not participate in decisions or deliberations of the ESCRO Committee.

Meeting Attendees. In addition to attendance by ESCRO Committee and supporting administrative staff members at ESCRO Committee meetings, the Chairperson may invite persons with competence in certain aspects of hESC research or representing community perspectives to assist in the review of issues that require expertise beyond or in addition to that of ESCRO Committee members. Non-voting attendees may include, on an ad hoc basis, the UW’s designated Institutional Official, representatives of the Washington Attorney General’s Office, and representatives from other UW research oversight committees and UW administrative offices. Attendance by other persons at meetings of the ESCRO Committee shall only be at the invitation of and with the permission of the Chairperson in consultation with other ESCRO Committee members.

Responsibilities.The ESCRO Committee’s review shall be specific to the scientific and ethical issues presented by proposals to use hESC in particular research projects. ESCRO Committee review and approval shall be deemed to be separate from and in addition to any other reviews or approvals otherwise required at the UW for such research, including but not limited to committees or administrative offices having responsibility for review and approvals of human subjects research, animal research, biological safety, radioactive materials, and environmental safety. The responsibilities of the ESCRO Committee shall be to:

Provide, in accordance with GIM 36, scientific and ethical review of proposed hESC research, including compliance with applicable regulatory requirements and UW policies;

Review and approve or disapprove all hESC research at the UW or involving UW personnel requiring institutional review (subject to any other UW approvals that may also be required);

Provide continuing review and approval of all hESC research requiring institutional review, including review of progress, adverse events, and similar reports that may be submitted to the UW by investigators conducting hESC research;

Confirm that the provenance of hESC used in hESC research at the UW or involving UW personnel is adequately demonstrated, and when appropriate, confirm that there is IRB approval of the process for acquisition of hESC to verify adherence to basic ethical and legal principles of informed consent and protection of confidentiality;

Refer to and require review of research proposals by other oversight offices or committees as required by UW policies, including but not limited to those relating to human subjects research (IRB), animal research, biological safety, and conflicts of interest;

Prescribe, establish and maintain a registry of hESC lines maintained at the UW;

Prescribe, establish and maintain a database of ongoing hESC research at the UW, including information regarding key personnel, the type of hESC research, and the hESC in use;

Monitor national, state and local ethical, regulatory and policy discussions regarding hESC research and from time to time propose modifications to UW policy as needed;

Adopt, implement and publish rules of procedures that are consistent with GIM 36 and other UW policies governing the conduct of ESCRO Committee affairs and interactions by investigators with the ESCRO Committee, including but not limited to rules covering: quorum requirements; conflict of interest disclosures by members; meeting format, schedules and length; workload assignments; content of minutes; applications and other forms; criteria for evaluating hESC research proposals; and communication of decisions; and

Facilitate education and training of investigators in the policy, ethical, legal, regulatory, and compliance issues involved in hESC research, including recommending minimum compliance training requirements as a condition for participating in hESC research;

Review Standards. ESCRO Committee review shall be primarily directed to determining whether proposed hESC research is scientifically meritorious and ethically acceptable. The ESCRO Committee shall only approve hESC research proposals whose goals are judged to be scientifically worthy and whose methods demonstrate sound research design, such that it can be reasonably expected that the study is likely to answer the proposed questions and to achieve the stated goals of the research. In so doing, the ESCRO Committee shall take into account the inherent uncertainty of the outcome of scientific research while also assessing the overall importance or significance of the proposed research. In carrying out its review, the ESCRO Committee shall give substantial consideration to any ethical or social aspects of the proposed research and shall not approve any proposal that is inconsistent with the prohibitions set forth in the section Prohibited hESC Activites of GIM 36 or otherwise fails to meet generally accepted ethical principles for the conduct of hESC and other research. In accordance with the ESCRO Committee’s rules of procedure, an investigator proposing to conduct hESC research will be required to provide the ESCRO Committee no less than a detailed description of the proposed research, adequate documentation demonstrating the provenance of hESC and hESC lines to be used in the research, and evidence of compliance with other required reviews. In cases where a proposal fails to meet the requirements of GIM 36, the ESCRO Committee Chairperson may disapprove the application without review by the full ESCRO Committee. In making determinations, the ESCRO Committee shall have authority to grant full conditional approval (subject to obtaining all other required UW approvals), conditional approval (such to specific conditions, limitations, or changes) or disapprove proposed hESC research. The ESCRO Committee may also establish rules and procedures by which applications may be reconsidered or resubmitted with substantial revisions.

Conflicts of Interest.

Researcher Significant Financial Interests. All investigators participating in hESC research shall disclose personal financial interests in accordance with the UW’s Significant Financial Interest Disclosure Policy, GIM 10. The ESCRO Committee research proposal application shall include questions, comparable to those on the UW’s human subjects research application, representing and affirming compliance with GIM 10 by investigators proposing to participate in hESC research.

ESCRO Committee Member Conflicts of Interest. It shall be the responsibility of each ESCRO Committee member to disclose all personal, financial, and other competing interests that could reasonably be seen as affecting the ability of the committee member to impartially discharge the committee member’s duties. Potential conflicts include but are not limited to personal financial interests, professional interests, or personal relationships having a significant connection to a matter under consideration by the ESCRO Committee. The ESCRO Committee as a whole shall determine whether and the extent to which a disclosure disqualifies the committee member from participating in the review of a particular matter under consideration.

Coordination with UW Institutional Review Board

To ensure consistent and efficient processing of hESC research proposals requiring IRB review, the UW Human Subjects Division shall designate a single IRB committee as having exclusive jurisdiction to review all hESC research proposals requiring IRB approval. In carrying out their reviews, the IRB and ESCRO Committee shall strive to coordinate their activities to avoid unnecessary overlap and duplication of reviews and shall cooperate in the sharing and interchange of information to the extent permitted by applicable rules and regulations.

Procurement and Transfer of hESC and hESC Lines

Investigators shall procure hESC and hESC lines consistent with GIM 36 and UW purchasing rules and regulations. Upon procurement, the Principal Investigator having authority over such newly-acquired hESC and/or hESC lines shall promptly transmit required information to the ESCRO Committee for entry into the UW hESC registry described in section Establishment of UW hESC Registry below. hESC and hESC lines shall only be transferred to other investigators, both at the UW and outside the UW, and to other organizations consistent with the provisions of GIM 36 and other applicable UW rules and regulations.

hESC Derived Cell Lines and Derivatives

Creation and Transfer of New hESC Derived Cell Lines. NIH guidance states that creation of hESC derived cell lines from hESC lines that are not on the NIH hESC registry is considered ineligible hESC research and may not be supported by federal funds. To ensure compliance with federal restrictions applicable to the creation and use of new hESC lines, all PI’s who are authorized to create new hESC derived cell lines must also (i) maintain adequate records in order to enable the UW and the PI to demonstrate the provenance of such cell lines, (ii) upon creation, promptly transmit required information to the ESCRO Committee for entry of the newly created hESC line into the UW hESC registry described in section Establishment of UW hESC Registry below, and (iii) restrict new uses or transfer of new hESC derived cell lines until obtaining any required approvals from the ESCRO Committee and other UW offices.

Use of New hESC Derived Cell Lines. Prior to using any new hESC derived cell line, irrespective of source, the PI must ascertain the provenance of the hESC line, including whether the hESC line originated from an approved hESC line. In conducting hESC research involving a new hESC derived line, the following rules must be followed:

hESC Derived Cell Lines Derived from NIH hESC Registry Lines. hESC derived cell lines created from approved hESC lines may be used for subsequent federally funded research, providing the subsequent use is consistent with the terms of the grant or other support provided to create the hESC derived cell line. hESC derived cell lines that are created from approved hESC lines that are restricted by the federal government for use in non-federally funded research may be allowed for such use provided the costs of the hESC derived cell line are not charged to the federal government and the federal grant does not prohibit use of the hESC derived cell line for non-federally funded research. If the nature of the hESC derived cell line is such that estimating their costs is not feasible, the hESC derived cell line may be used where:

the hESC derived cell line is not needed to carry out the federally funded project.

the school or college, in consultation with OSP, approves the use of hESC derived cell line from federally funded research based after OSP has reviewed the terms of the federal grant; and

the federal government is not charged for any cost associated with use of the hESC derived cell line in non-federal research.

hESC Derived Cell Lines Derived from non-NIH hESC Registry Lines. Costs associated with research on hESC derived cell lines created from hESC lines not listed on the NIH hESC registry (including personnel and equipment) may not be charged to federal sources, even if such research is undertaken in whole or part to benefit a federally funded project.

Use of hESC Derivatives, Data, and Intellectual Property. Except to the extent prohibited or restricted by federal law or rules or by the terms of financial support of research supporting their creation, UW investigators may use hESC derivatives, data, and intellectual property in any hESC research, providing the research is in accordance with GIM 36 and any other applicable UW policies, rules and procedures.

Establishment of UW hESC Registry

Through the establishment of a centralized registry prescribed by the ESCRO Committee, the UW will maintain a record of all hESC lines, including new hESC derived cell lines, kept at UW facilities. The UW hESC registry will be supported and maintained within the UW Office of Research and will contain information about the source and provenance of hESC lines, the location of the hESC lines, the name of the investigator responsible for the safekeeping of the hESC, disposition of hESC lines, and such other information the ESCRO Committee deems appropriate.

Establishment of UW hESC Research Database

Through the establishment of a centralized database prescribed by the ESCRO Committee, the UW will maintain a record of all hESC research both occurring in UW facilities or involving UW personnel. In cooperation with OSP and the UW’s System to Administer Grants Electronically (SAGE), the UW hESC research database will be supported and maintained within the UW Office of Research and will contain information identifying the investigators conducting hESC research, including the PI, the funding source of the research, OSP and other relevant UW identifying numbers, the period of the research, a brief description of the research, and such other information the Vice Provost for Research deems appropriate.

hESC Tissue Banks and Repositories

Any tissue banks or repositories at the UW containing hESC and hESC lines, including new hESC derived cell lines, shall be subject to subject to the requirements of GIM 36 and shall be included within the UW hESC registry described above.

hESC Researcher Compliance Training

As a condition of and prior to conducting hESC research, investigators are required to be familiar with applicable UW and other compliance policies, rules and regulations governing such activity, including GIM 36. The ESCRO Committee will recommend to the Vice Provost of Research a hESC compliance training program that will be sufficient to demonstrate knowledge of these policies. The content of such training shall include information on categories of hESC research, requirements for ESCRO Committee reviews, documentation of compliance, permitted and prohibited use of federal funds, human subjects research issues, and such other matters the ESCRO Committee deems appropriate. The training program shall provide instruction by means of a one-hour seminar, either delivered in person, online or through written materials.

Intellectual Property and Technology Transfer

Inventions and Discoveries. Intellectual property discovered or created by UW investigators in the course of hESC research will be disclosed to UW TechTransfer in accordance with the UW Patent, Invention, and Copyright Policy (http://www.washington.edu/faculty/facsenate/handbook/04-05-07.html). All intellectual property arising from hESC research shall be managed in accordance with the foregoing policy and the rules and procedures of UW TechTransfer. Consistent with the foregoing, the UW recognizes that there may be instances in which it will be in the public interest to place intellectual property arising from hESC research in the public domain or by broad non-exclusive licensing. Decisions in such cases shall be made by UW TechTransfer after appropriate consultations with the hESC investigators.

UW Institute for Stem Cell and Regenerative Medicine

The UW Institute for Stem Cell and Regenerative Medicine (ISCRM) has been established for the purpose of facilitating and encouraging basic research on hESC in order to develop therapies and cures for human disease. In making decisions about policies and procedures governing the conduct of hESC research, the UW and the ESCRO Committee will provide reasonable opportunities for investigators who are part of ISCRM to express their views on such matters and take into account such views in making decisions. The ESCRO Committee and ISCRM will strive to cooperate in establishing efficient mechanisms for review of hESC research proposals and the training of hESC research investigators.

Appendix: Cost Allocation Guidelines

Introduction

Financial Definitions

General Cost Allocation Principles

Application of Federal Cost Principles to Specific Resources

Further Questions and Information

Introduction

In order to carry out ineligible hESC research at the UW, the UW is required to maintain careful records documenting that no federal funds are used, either directly or indirectly, to support research involving the use of hESC not listed on the NIH hESC registry.

The UW is providing these guidelines, which are consistent with federal hESC research restrictions, in order to set forth the steps that researchers and administrators can take to ensure that hESC research can proceed unimpeded at the UW. These guidelines describe steps to take in managing resources used for hESC research, including (1) facilities, (2) equipment, (3) personnel, (4) materials, supplies, and other commodities, (5) non-capitalized equipment, (6) purchased services, (5) derivatives from hESC research, and (6) data and intellectual property associated with hESC research.

These guidelines are intended to address only those issues presented by current federal hESC research policy. They supplement, but do not replace, other UW financial and accounting policies, rules and procedures.

Financial Definitions

In addition to the definitions set forth in Section IV, Definitions, above, the following definitions shall apply to these cost-allocation guidelines:

Indirect costs incurred for common or joint objectives that cannot be identified readily and specifically with particular sponsored projects and instructional activity or any other institutional activity.

materials, supplies, and other commodities

Consumable goods and reusable items, including laboratory supplies and equipment, with an acquisition cost of less than $2,000 ($5,000 for recharge and cost centers) and an expected useful life of one year or less.

non-capitalized equipment

Reusable items, including laboratory supplies and equipment, with an acquisition cost of less than $2,000 (less than $5,000 for recharge and cost centers) and an expected useful life of more than one year.

purchased services

Professional contract services, such as the services of consultants, laborers, or maintenance and repair technicians.

General Cost Allocation Principles

The cost principles set out in 2 CFR 200 do not prohibit institutions that receive federal support from engaging in “unallowable” activities. Instead, they restrict the use of federal funds to pay for these activities. For example, Subpart E-COST PRINCIPLES of 2 CFR 200 states that the costs of bad debts, donations and contributions, and entertainment (among others) are generally unallowable. Thus, while researchers may make a personal choice to celebrate a colleague’s accomplishment at a local restaurant, it is not appropriate to charge the cost of that celebration to the federal government. Even though certain costs are unallowable, the UW and its researchers may still be reimbursed for other allowable expenses incurred in connection with federally supported projects.

Subpart E-COST PRINCIPLES of 2 CFR 200 indicates that a federally-supported institution can avoid the impermissible shifting of costs of unallowable activities to the federal government if it does not either (1) impose the direct costs of such activities on the federal government, or (2) request reimbursement from the federal government for F&A costs associated with unallowable activities. Examples of indirect costs are building depreciation, maintenance expenses, library expenses, and student and departmental administration expenses.

Direct Costs

To determine whether a particular direct cost can be charged to the federal government, the cost must be allowable, reasonable, and allocable to work conducted under federally sponsored agreements, and it must not include any unallowable costs.

Although the direct costs of unallowable activities may not be charged to the federal government, the government will pay its share of resources that are used for both federal and non-federal purposes. Subpart E-COST PRINCIPLES of 2 CFR 200 states that “a cost is allocable to a particular cost objective (i.e., a specific function, sponsored agreement, department, or the like) if the goods and services involved are chargeable or assignable to such cost objective in accordance with relative benefits received or other equitable relationship.” For example, if personnel time or general-purpose laboratory materials are being used for both federally sponsored research and ineligible hESC research, the federal government will pay the cost of that proportion of the resource being used for federally sponsored research.

Indirect Costs

In general, UW F&A costs are calculated and allocated to the federal government by multiplying the direct costs of a federal project by the government-approved UW F&A rate. This approach assumes that there is an established relationship between the direct costs of research projects and the F&A costs as reflected in the F&A rate and that it is therefore possible to identify the F&A costs associated with a particular project by applying the predetermined rate to the total amount of direct costs associated with the project. The NIH guidance on hESC research indicates that the indirect costs of ineligible hESC research are subject to this approach. As a result, the costs of ineligible hESC research may be included in the regular F&A cost allocation base, and associated indirect costs may be allocated pursuant to ordinary cost allocation principles. The NIH Frequently Ask Questions on this subject states that compliance with these methodologies “will prevent the shifting of unallowable stem cell research costs to federally sponsored programs.”

Application of Federal Cost Principles to Specific Resources

In addition to obtaining required approvals to conduct hESC research, a PI engaged in ineligible hESC research must obtain confirmation from the PI’s school or college that the proposal conforms to the guidelines set out below.

These cost-allocation guidelines apply to facilities, equipment, personnel, materials, supplies, non-capitalized equipment, and purchased services, devoted in whole or part to eligible or ineligible hESC research, regardless of funding source. The schools and colleges are responsible for implementing the guidelines for these specific resources, in consultation with OSP, including recharge and cost centers involved in hESC research activities.

Facilities

UW facilities may be used to conduct hESC research only if they are approved for that use in advance. NIH guidance specifically provides that an investigator receiving NIH support may create new hESC derived cell lines and engage in other ineligible hESC research providing (i) all direct costs of such activities are allocated to a non-federal funding source, and (ii) the UW has in place a reasonable method of separating costs so that the appropriate F&A costs allocable to the ineligible hESC research are allocated to non-federal accounts so as to prevent federal funds from improperly supporting ineligible hESC research. Prior to commencing hESC research, the PI must (i) have written confirmation from the school or college that the facility has been approved for use in the conduct of hESC research, and (ii) adhere to any limitations contained in the written approval regarding the usage of facilities and related recordkeeping. The following guidelines apply to the approval of facilities in which hESC research is conducted:

Responsibility for Seeking Approval. The PI retains primary responsibility for seeking approval for facilities to be used in the conduct of hESC research.

Tracking Usage of Facilities. UW’s existing policies and procedures for tracking and confirming the usage of facilities for federally funded research, and the direct and indirect costs associated with that usage, will apply so that only allowable costs are charged to federal grants, and so that the costs of using facilities for other activities, including ineligible hESC research, are not supported by federal funds.

Limitations on the Usage of Facilities. UW facilities may be used for ineligible hESC research, subject to approval on appropriate conditions. Such conditions may include, for example, limitations on time, allocation of space, or percentage of use and will in any event take into account other commitments for the facilities, if any, to federally sponsored projects and to other UW activities, including non-federally sponsored research.

Use of Multiple Facilities. As part of the approval process, the PI must disclose all locations, both on-campus and off-campus, where any hESC research, including ineligible hESC research, will be conducted.

Approval of Changes in Usage of Facilities. Any change in space usage where ineligible hESC research is conducted, whether addition or deletion of existing space, or changes in time or percentage of ineligible hESC research or other usage, is also subject to these guidelines. Changes must be reviewed and approved by the school or college, in consultation with OSP, in accordance with usual and customary procedures.

Equipment

UW equipment may be used to conduct ineligible hESC research with advance approval of the school of college. According to current NIH guidance, the acquisition of equipment used in the conduct of ineligible hESC research may not be federally supported. Federal regulations (45 CFR §§ 75; 2 CFR 200.313) contain additional rules that restrict the use of federally-owned equipment or other equipment acquired with federal funds. Prior to commencing hESC research, the PI must (i) have written confirmation from the school or college that the equipment has been approved for use in the conduct of hESC research and (ii) agree to any limitations in the written approval regarding the use of equipment and related recordkeeping. Limitations may involve, for example, restrictions on time or percentage limits on equipment capacity. The following guidelines apply to the approval of equipment to be used in hESC research:

Responsibility for Seeking Approval. The PI retains primary responsibility for seeking approval for equipment, whether existing or proposed for acquisition, to be used in the conduct of hESC research.

Tracking Usage of Equipment. UW’s existing policies and procedures for tracking and confirming the acquisition and usage of equipment for federally funded research, and the direct and indirect costs associated with acquiring and using equipment, will apply so that only allowable costs are charged to federal grants, and so that the costs of acquiring or using equipment for other activities, including ineligible hESC research, are not supported by federal funds.

Usage of Equipment. The school or college, in consultation with OSP, will issue approval as follows:

Equipment Owned by UW. Equipment owned by UW may be used to conduct ineligible hESC research if the following conditions are satisfied:

Acquisition of the equipment was not supported by federal funds, and

Use of the equipment is not subject to any other restrictions, including restrictions imposed by non-federal sponsors.

Equipment Owned by the Federal Government. Equipment owned by the federal government may be used in conducting ineligible hESC research only in the following circumstances:

Use of the equipment is expressly permitted pursuant to the terms of the federal award under which the equipment was obtained, the terms of an equipment rental agreement, or the approval of the appropriate federal agency; or

UW purchases the equipment from the federal government and has documentation of such transaction, including title transfer.

Equipment Owned by UW but Purchased with Federal Support. Equipment owned by UW but acquired, in whole or in part, with federal funds may be used in conducting ineligible hESC research only in the following circumstances:

All competitive segments of the federal grant or contract supporting the equipment purchase have been completed and UW retains title to the equipment without restriction, observing any preferences for federal usage; or

Use of the equipment for ineligible hESC research is permitted pursuant to the terms of the federal grant or the approval of the appropriate federal agency; or

UW purchases the equipment in full, without federal restriction, and has documentation of such transaction.

Approval of Changes in Usage of Equipment. Any anticipated changes in usage of equipment are also subject to these guidelines. Changes must be reviewed and approved by the schools, in consultation with OSP in the usual and customary fashion.

Personnel

As provided in GIM 36, all UW personnel participating in hESC research must have prior approval from the UW regardless of whether the research is eligible for federal funding and whether any of the personnel receive federal funding for any purpose. Prior to commencing hESC research, the PI must (i) ascertain that any required approvals have been obtained from the ESCRO Committee, (ii) obtain written approval on Form eGC-1 from the school or college to conduct the research, and (iii) obtain the agreement of all UW personnel participating in the hESC research to follow all UW rules and procedures regarding hESC research, including GIM 36 and these hESC cost-allocation guidelines. In addition to the foregoing, the following rules apply to the approval of personnel to participate in hESC research, regardless of funding source:

Responsibility for Seeking Approval. The PI shall have primary responsibility for ensuring that approvals are sought and obtained for all personnel participating in hESC research.

Tracking Effort. UW’s existing policies and procedures for tracking and confirming work effort, both direct charged and cost shared, on federally funded research will apply so that appropriate effort is devoted to commitments under federal grants, and so that other activities, including ineligible hESC research, are not supported by federal funds (See GIM 35 – Effort Reporting Policy for Sponsored Agreements).

Support and Cost Sharing. Non-federal funds may be used to support all hESC research, including ineligible hESC research. Effort expended on ineligible hESC research cannot be used to meet cost share commitments to federal projects.

Allowable Effort. The total effort commitment of an individual requesting approval to work on ineligible hESC research may not exceed 100%, taking into account the individual’s existing commitments, any allowable adjustments thereto, and the individual’s proposed hESC research commitment. The total allowable amount of committed effort for faculty members or others with teaching and administrative responsibilities may also be less than 100% in accordance with school or college policy.

Individuals Holding Multiple Appointments. Many UW personnel have appointments or relationships elsewhere, including with affiliated hospitals and other institutions. The process for approving UW personnel to engage in hESC research will consider in the usual and customary fashion other appointments, relationships, and commitments of such personnel.

Work Benefiting Multiple Research Aims. From time to time, certain research activities may require further analysis to determine whether they may be supported in whole, part, or not at all by federal funds. Research activities on approved hESC lines may be supported by federal funds to the extent permitted by the particular grant. Ineligible hESC research may not be supported by federal funds. On occasion, certain types of activities may be directed to research aims with respect to approved hESC lines and hESC lines not listed on the NIH hESC registry, for example, the development of a reagent or assay that can be used on both types of hESC lines. In such instances, time and effort performing such activities should be allocated in proportion to the benefit each receives.

Approval of Changes in Effort Commitments. The PI retains primary responsibility for seeking appropriate approvals if there are any changes in time and effort commitment to the sponsor on hESC research. The school or college will review and approve any such change requests, in consultation with OSP.

Materials, supplies, non-capitalized equipment, and purchased services owned or acquired by UW may be used in conducting ineligible hESC research. Prior to commencing hESC research, the PI must (i) determine, for cost-allocation purposes, which materials, supplies, non-capitalized equipment, and purchased services were purchased specifically to carry out ineligible hESC research, (ii) agree to recordkeeping requirements for tracking the usage of general-purpose materials, supplies, non-capitalized equipment, and purchased services, to ensure that the federal government is not charged for ineligible hESC research. The school or college, in consultation with OSP, is responsible for ensuring that these requirements are followed. For acquired materials, supplies, non-capitalized equipment, and purchased services this should be done through separate budgets and/or other appropriate financial accounting methods. The following guidelines apply to the usage of materials, supplies, and purchased services:

Consumable Materials and Purchased Services.

Specific Purchases. If purchased services, such as the services of consultants, laborers, or maintenance/repair technicians, or purchased materials are used to carry out ineligible hESC research, neither the direct costs of those items nor the indirect costs associated with their acquisition may be charged to the federal government.

Use of Materials from General Supply. Materials withdrawn from general supply should be charged at their actual net cost “under any recognized method of pricing inventory withdrawals, consistently applied.” (OMB Circular A-21, at J.31.) Transportation charges may be included. The PI must track usage and apply a written plan for allocating costs among different projects. In such cases, the indirect cost must be transferred as well. For example, if a the PI of an ineligible project desires to consume one-half of the cost of existing materials initially purchased with federal funds for $100, then the $50 of the Materials plus the associated indirect costs must be transferred to non-federal sources prior to using or consuming the materials.

Non-Capitalized Equipment. The cost of non-capitalized equipment must be allocated among the projects for which they are used, under a reasonable allocation plan consistent with UW policies.

Data, Information and Intellectual Property Obtained from hESC Research

Researchers may use data, information and intellectual property obtained from any hESC research in subsequent hESC research, regardless of whether the subsequent projects are federally or non-federally funded. However, the federal government may not be charged for generating data from ineligible hESC research, or for analyzing or manipulating data for subsequent use in ineligible hESC research. These cost-allocation guidelines govern the determination as to whether resources engaged in the generation, analysis, or manipulation of data from hESC research may be charged to the federal government. Any use of data is subject to the usual consideration of third-party intellectual property rights, as well as any specific grant or contract constraints on data usage imposed by the suppliers or sponsors of the data, including other research institutions and federal funding agencies.

Further Questions and Information

These cost-allocation guidelines are subject to revision in light of any changes in law, rules or regulations. Any questions about these guidelines and their application to specific research projects should be referred through the school or college. In addition, specific questions about costing issues for grants, cost centers, and recharge centers should be referred to the UW Office of Grant and Contract Accounting, Management Accounting and Analysis. In order that UW personnel do not receive conflicting or incomplete information, formal inquiries on behalf of the UW to federal agencies about the application of federal cost principles to hESC research shall be made by OSP.